Anthrax toxin protective antigen protein (PA) binds to receptors on the surface of mammalian cells, is cleaved by cellular proteases, forms an oligomer, and transports two other toxin proteins, lethal factor (LF) or edema factor (EF) to the cytosol. EF is a potent calmodulin-dependent adenylyl cyclase that causes large increases in intracellular cAMP concentrations. LF is a metalloprotease that cleaves several mitogen-activated protein kinase kinases (MEKs) and the N-terminus of the inflammasome sensor NLRP1. The inflammasomes are intracellular complexes that play a role in innate immune sensing for defense against pathogens. The cleavage of NLRP1 in macrophages and dendritic cells leads to caspase-1 activation and a rapid cell death termed pyroptosis. Caspase-1 activation, which is the resultant effect following activation of many other inflammasome sensors, including the NLRP3, NAIP/NLRC4 and AIM2 sensors, also leads to maturation and release of the pro-inflammatory cytokines IL-1 and IL-18. The inhibition of the MEK pathways has a wide range of consquences for the host, but also allows the development of toxin-based anti-cancer therapeutics for targeting of MEK-dependent tumor cells. In the last year, in collaborative studies using rat aortic ring models, challenge with edema toxin (ET) was shown to reduce phenylephrine-induced contraction. This effect was shown to be dependent on nitric oxide (NO) production, as L-nitro-arginine methyl ester (L-NAME) reduced ET effects on contractile force. L-NAME also increased survival of rats challenged with a lethal dose of ET in a manner correlated to reduction of circulating NO levels. Furthermore, L-NAME reduced mean arterial blood pressure in toxin-treated rats. These studies demonstrated that NO production contributes to ET's arterial relaxant, hypotensive and lethal effects. In another collaborative study, the inhibitor effect of LT on the MEK pathway was analyzed in malignant astrocytoma cells. LT was not toxic to astrocytoma cells, but instead caused a significant decrease in cell motility as shown in wound healing models, 2D motility in serum and reduced invasion of cells across collagen matrices. LT effects on cell migration were mediated through deregulation of Rho GTPases and could be mimicked by inhibition of MEK pathways. This study represented the first report of LT on cancer cell motility and invasion, suggesting the toxin could be developed as a potentially selective brain tumor invasion inhibitor. Finally, as we continued our studies on anthrax LT effects on the Nlrp1 inflammasome both in cell systems and in vivo, we synopsized the literature on bacterial exotoxin activation of different inflammasomes in a comprehensive review of current research in this area.